Why You’re Aging Faster Than You Think & How to Slow It

I’ve been looking forward to sharing this conversation with you because it’s one I’m truly passionate about. Today, we’re diving into the DunedinPACE epigenetic clock with one of its creators, the brilliant Dan Belsky. It’s a tool I use regularly with my patients, and one that’s transforming how we approach aging and interventions. While this episode is a bit more technical than usual, the science is fascinating, and the real-world applications are incredibly valuable. This isn’t just about theory—it’s about practical insights that can change how we measure aging and track the effectiveness of the treatments we offer. Stick with us, and you’ll walk away with actionable knowledge that can make a difference in your practice.  ~DrKF

Why You’re Aging Faster Than You Think & How to Slow It

In this episode of New Frontiers in Functional Medicine, Dr. Kara Fitzgerald interviews Dr. Dan Belsky, PhD—renowned epidemiologist and co-creator of the DunedinPACE biological aging test. Together, they explore the science of aging, including how molecular damage drives biological decline and how epigenetic clocks like DunedinPACE are transforming the way we measure and manage aging. Dr. Belsky shares insights on caloric restriction, psychological resilience, and personalized longevity strategies, offering clinicians a deeper understanding of how to use aging biomarkers to optimize healthspan and deliver more targeted care.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine and today, of course, is no exception. If you’re with me on YouTube, you will see that I am sitting next to Dr. Dan Belsky, one of the creators of the Pace of Aging test that many of us are now using in practice routinely. So we’re going to get to do a drill down into that, which I’m really quite excited about. But before we jump in, let me give you his background.

Dr. Kara Fitzgerald: Dr. Belsky is an associate professor of epidemiology at the Columbia University Mailman School of Public Health and the Robert N. Butler Columbia Aging Center. His work seeks to develop methods to measure the pace and progress of biological aging in humans and to use these methods to identify drug behavior and policy interventions that can address disparities in healthy aging and increase healthy lifespan for all. He is an inventor of the Pace of Aging method and the DunedinPACE of Aging epigenetic clock. And I want to add that he is the 2025, so this year’s Vincent Cristofalo Rising Star scientist for aging research. Dan, welcome to New Frontiers.

Dan Belsky, PhD: Thanks for having me.

Dr. Kara Fitzgerald: First of all, I want to get your perspective on what biological aging is.

Dan Belsky, PhD: Sure. I think you ask scientists and they’re going to tell you as many things as the scientists you ask, but where we come from, and I think a reasonable consensus in people who work in the space of the field that I work in, is that we think of biological aging as the progressive loss of integrity and resilience capacity in cells, tissues, and organs that accumulates as we get older, ultimately makes us sick, and kills us. So there is a sort of molecular level explanation you’ll get from people who do biochemistry, there’s a functional explanation that you’ll get from people who are geriatricians, and there’s everything in between. But we tend to think about it as this is the way in which my health deteriorates as I get older and we see that as arising from an accumulation of molecular damage that really breaks us at every level of biological organization.

Dr. Kara Fitzgerald: Okay, good. And that’s what we’re going to focus on, but I want to juxtapose that with actually something you said in a lecture I was listening to recently where we can also look at aging from this sociological perspective. We juxtapose the fact that I’m a better person now in my 50s. I think my heart is more open, I’m more patient with my kid, et cetera. I sort of have this maturation process that has occurred that’s favorable even as my joints might be a little more creaky. Thoughts on that?

Dan Belsky, PhD: Yeah, so I sit in an interdisciplinary aging center in which we have social gerontologists, we have biogerontologists like myself, there’s an evolutionary biologist next door, and so aging means many things to many different disciplines and we shouldn’t lose sight of the fact that as we grow older, we grow, we change, we develop social and psychological assets that may help us better navigate the world, and even better protect our health at the same time as we’re experiencing this, sort of, degradation in core biological functions within our body. And we should value, in some sense, as my dean here likes to call them, the assets of aging, even as we seek to combat the depredations of aging at the cellular and tissue levels. And just to speak to those sort of assets very briefly, I mean, you mentioned our hearts are more open. So that’s absolutely true.

Dan Belsky, PhD: And another observation that’s been made about people as they get older is we are better at delaying gratification, acting planfully, being patient with the world. And as anyone who’s ever tried to adhere to a dietary or exercise regimen, or even just keep their blood pressure down in traffic knows, those kinds of things are hard and important. So thinking about how we can build up those assets of aging may ultimately prove to be an important part of the geroprotective strategy that we use to delay biological aging and preserve healthy lifespan.

Dr. Kara Fitzgerald: Awesome.Thank you so much for that. Yeah, because we do want to hang on to the fact that there’s some beautiful stuff that transforms in this process of maturation, even as we want to zero in on the deterioration and turn it around. Okay, so moving back to the breakdown process that you’re focused on, how do we best measure that?

Dan Belsky, PhD: This is a question near and to my heart, of course, and again, there are many different answers. We have chosen to approach the study of this breakdown by measuring changes that occur in people’s bodies, beginning with readouts on the functioning of different organ systems. There are alternatives, so you can think about lifespan as being the coarsest, but perhaps the most definitive benchmark for how fast that’s happening. There are losses of functional capacities that we can focus on, and in particular if you’re dealing with people who are in the later stages of their life, those can in fact be quite sensitive and specific readouts on the progression of the aging process.

Dan Belsky, PhD: But when we’re looking at people who are still in the middle years of their life, who may not yet be developing chronic diseases, when we want to track that process of biological deterioration in people that are just moving around in the world, who are trying to measure without doing terribly invasive things to them, we think that accumulating information on the functioning of their organs from blood biomarkers or tests like spirometry, where we’re testing your lung function or taking your blood pressure, is a really important window into that process.

Dan Belsky, PhD: And what we have learned from our work over the past decade is that you can start with those measurements of how people’s bodies are functioning and build down from there into observations of their cells. And today, the way we are going about measuring the pace and progress of this thing that we call biological aging is using molecular tests, typically applied to blood although increasingly people are starting to think about saliva, that we think reflect what’s going on at the organ and tissue level, which in turn is reflecting this accumulation of molecular changes within and between our cells that really are the causal agents in that breakdown of integrity and resilience capacity that is the heart of aging.

Dr. Kara Fitzgerald: I’ll throw out a few questions and I’ll just let you move through them. We want to talk about what the Pace of Aging is, what the extraordinary tool is that you guys started to develop, I think you first published on it in 2015, so we can go into that particular clock for measuring aging, and whether or not clock is the appropriate term for it. And it’s a DNA methylation clock, and most of my audience are familiar with DNA methylation clocks. We’ve been talking about them for years, but it’s based on these biomarkers that you’ve just mentioned. And you have said that ultimately, the Pace of Aging, the tool, is more effective at identifying the aging journey, at picking up those molecular changes associated with deterioration that is biological aging, than those markers. So I want to talk about that as well. So let me throw that big question out, or big multi-stepped question.

Dan Belsky, PhD: Sure. So, building from that sort of general observation, this is how we think about it. The particular tool that we have spent a number of years working on we call DunedinPACE and it’s an epigenetic clock, to the extent people are familiar with this. So it’s an algorithm that combines information about DNA methylation from 173 different positions on the genome into a single number. And that number is reflecting the years of biological aging that you experience for each 12-month calendar interval. And DunedinPACE was derived in the Dunedin Longitudinal Studies. Dunedin is a city in New Zealand. It is the home of the University of Otago, which is, I believe, the oldest university in New Zealand and the southernmost medical center in the world. So it’s this small city on the southeastern coast of the South Island of New Zealand.

Dan Belsky, PhD: In 1972-1973, there was a study undertaken at that university of essentially the cost of childbirth. It was part of a national study that was interested in understanding how much it was going to cost when they rolled out a national health service and were paying for everybody to have a baby. And some enterprising pediatricians and developmental psychologists at the University of Otago decided, hey, we can turn this into a cohort study and follow up these kids when they turn three. And they came back when they were five and they started to recruit their colleagues and others to the study and it grew to the point where we are now 50 years into the study. It’s led by a team at the University of Otago, Moana Theodore is the current director. Richie Poulton, who was the director at the time we did our study has unfortunately passed, and co-directed by my collaborator, Terry Moffitt and her husband, colleague, Avshalom Caspi who lead the sort of American funding into the Dunedin study.

Dan Belsky, PhD: And so the Dunedin study, over these 50 years, has tracked every aspect of the lives of every baby who was born in that hospital in that 12-month calendar interval. And they’ve been able to retain almost all of them in the study over that half century of follow-up. Phase 52 is not done yet, but as of Phase 45, 95% of the surviving study members were still participating. And this is through the truly heroic efforts of the research team who do things like send people plane tickets to fly them back from wherever in the world they’re living so they can participate or go visit them if they won’t come back, as well as the mothers of the study members, who I’ve learned are sort of really the beating heart of the thing, although they’re now much older and some of them have since passed. This effort to retain the cohort gave us, when it came time for us to do our study, this incredible resource in which we could observe changes occurring in the bodies of a complete population cohort essentially, over a period in the case of our first study of 12 years.

Dan Belsky, PhD: And if you’re using DunedinPACE, that’s based on an analysis that extended for an additional seven years, so it’s about two decades of follow-up, without bias from the kinds of processes that contaminate most of the other longitudinal studies that people like me work with. So what we’re used to is you recruit a cohort of people, and then you bring them back the second time, and you lose maybe half, maybe 40% of them. You feel good if you keep 60% of them. Then you might lose another 20% and hopefully from there you may be stable or you lose a little bit here and there. This cohort has kept everyone. The reason that’s so important is that when we’re studying aging, our subject is a key cause of attrition. It is what is killing people, making them sick, changing them in ways they don’t want to continue to participate in research. So having this kind of unique population-based study really sort of grounded us in the right place to do the work.

Dan Belsky, PhD: What we were able to do in that initial study was take a comprehensive set of measurements of the physiology of these people, the kinds of measurements your doctor would take at your annual physical, plus a few that might have to be specially prescribed, like a VO2 max test, lung function assessment, and some more exotic biomarkers. But nothing particularly unusual. Telomere length was in our original draft. We had some lipid molecules that at the time were not routinely incorporated into standard clinical care, but you might get if you had a heart condition like your ApoB, or something like that.

Dan Belsky, PhD: We tracked these markers over the 12-year follow-up interval, and for each one, we were able to quantify for each study member how much faster or slower they were changing than the cohort norm. And again, that norm is really important to have a reference, and here it’s a population-based reference, so it’s a useful piece of information to center our expectation of what should be happening to a person. We could then combine information about how much faster or slower each of these biomarkers was changing into a single number, and then by comparing that sum to the norm for either the men or the women, depending on what the person was, we could form a ratio that we call the Pace of Aging. The years of physiological change they experience per year of calendar time.

Dan Belsky, PhD: And again, to think about the epigenetic clock, that wasn’t where we were when we first built this thing. We were aware of Steve Horvath‘s seminal paper. That was 2013, this paper came out in 2015. So we knew that was happening, but we were after something that we thought was a little simpler and that was, in our mind, closer to the thing that we were interested in changing with the goal of extending healthy lifespan. We wanted to slow the rate of change. And so I’ll talk a little bit more about why that rate of change is so important after I sort of walk through how we got to DunedinPACE. But what we discovered once we had built this thing and begun to make observations about it that reassured us it really was what we thought it was, was that it was awfully hard to get out of this unique and powerful cohort study and into the hands of clinical trialists who are testing therapies to slow aging, or physicians and patients who are interested in monitoring aging as part of healthcare.

Dan Belsky, PhD: And so that’s when we turned back to this question of the epigenetic clock. We had seen the work, Morgan Levine actually as a PhD student was a collaborator on that initial study, and by this time she had gone to Steve’s lab to do her post-doc and developed an epigenetic clock that many may be familiar with, called PhenoAge, where instead of asking can we predict whether a person is old or young from their DNA methylation in chronological time, she wanted to predict whether they were nearer or farther from dying. She was sort of flipping that around and I’ll talk a little bit more about that. But we thought we could borrow that same approach and instead of modeling risk of death in older people, we could model this rate of physiological change in young to midlife adults.

Dan Belsky, PhD: And that’s how we got from tracking changes in the bodies of a thousand New Zealanders to this DNA methylation blood test that your audience may be familiar with as DunedinPACE. And I said epigenetic clock before because that’s the term that everybody in the field uses. We would encourage people to refer to it as a speedometer. This is borrowing some language that I was introduced to by the biologist Richard Miller. And the idea of the speedometer is really that this is a readout not on how far you’ve gone, but about how fast you are going. And so when I’m writing and talking about this, I’ll often use the metaphor of a speedometer for DunedinPACE in contrast to an odometer for something like phenoage or GrimAge, which are really about marking your progress toward the end.

Dr. Kara Fitzgerald: So basically, you just had this incredible cohort, first of all. It’s extraordinary the consistency with which they’ve hung in there. I mean, a shout out to New Zealand and some of the science they do. It’s amazing. I’ve had a couple of people doing work associated with New Zealand on the podcast. And incidentally, Morgan Levine has been on the podcast as well and we’ll just bank all of that stuff in the show notes. In fact, I’ll put Dan’s bibliography in the show notes too, so you can access these papers that we’re referencing.

Dr. Kara Fitzgerald: So you guys were looking at all these incredible biomarkers on everybody, way beyond the scope of a physician’s office. Even a functional physician isn’t going to have a lot of the tools that you’re accessing, even though we’re doing a lot. And so then you had an aha moment on, maybe we can create a surrogate using the technology that’s originally been teased out by Steve Horvath, but now it’s gone beyond. And so that’s what you did and you’ve gone on to actually say that this surrogate that you’ve created outperforms the original measurements. Is that true?

Dan Belsky, PhD: Yes. I think what you’re referring to is an analysis that we published in the original paper where we were trying to make sense of our algorithm not having a perfect fit to what, in machine learning, we call the label, the thing that we’re training the algorithm to predict. So Steve’s original label was the time since birth to DNA methylation collection of his subjects, their age. Morgan’s label was a prediction of their mortality risk that she composed of their chronological age and some blood chemistry analytes. Our label was DunedinPACE.

Dan Belsky, PhD: So what we did was we took the biomarkers, we modeled change, then we took that change phenotype and we modeled it from the methylome. So we have this epigenetic surrogate of the change phenotype, then we took the change phenotype and the surrogate and we compared how well they could predict a set of functional outcomes. These measurements of strength, motor coordination, aged appearance and so forth. Those were not the biomarkers in the algorithm, those were the endpoints, essentially, that we’re using to evaluate whether the measurement of Pace of Aging was actually measuring aging or perhaps something else. And so what we found in the Dunedin study was that the DunedinPACE epigenetic speedometer was as good or better a predictor of people’s cognitive functioning, their strength, motor coordination, aged appearance as the original longitudinal phenotype.

Dan Belsky, PhD: So why would that be? You know, how could that happen? Because if you’re sort of an imperfect measurement of a thing, shouldn’t you be less good at predicting the stuff that that original thing was supposed to predict? And the answer is that any measurement that we take is going to have some combination of signal and noise in it. As physicians who interpret blood tests, you know that if my patient is experiencing systemic inflammation, their C-reactive protein will be elevated. But the particular number that you observe in their C-reactive protein measurement is not a perfect readout on their systemic inflammation. It’s integrating other information that may be less interesting to you, as we’ve learned perhaps, their genetic background may be influential of background level of CRP, but not consequential for risk of the things that we use CRP to measure risk for.

Dan Belsky, PhD: So in that way, when we model Pace of Aging, the longitudinal phenotype, with the DNA methylation data, our algorithm is only going to adhere to signal. The noise won’t vary systematically with methylation between people. And so the methylation algorithm is actually going to prove to be a distillation of signal from the original phenotype rather than just a sort of raw capture of it.

Dr. Kara Fitzgerald: Do we still continue with the original body of tools that you used? I mean, are we continuing to measure our lipids? It’s true that any physician looking at a battery of testing is going, to sort, of have internalized the wiggle room in a CRP, for example, or the fact that it’s acutely elevated because they got their blood drawn when they were sick, or whatever the case may be. And you might not be capturing the underlying inflammaging. Or as you pointed out, genetics could influence some of our labs. Of course they do. Are these tools still useful to us clinically or do we use both concurrently? Like, how do we think about this?

Dan Belsky, PhD: That’s a great question, but probably one better delivered to a practicing clinician than someone building these frontier tools for them to incorporate. I think from where I sit, there’s always going to be a place for measuring some of these conventional biomarkers in clinical medicine because they are highly predictive of clinical events that are deeply consequential to patients. I think that what this new set of biological aging tools, at least, is offering physicians is a new way of understanding whole person health and aging. And we see now people are building organ specific clocks, tissue specific clocks, you know, these kind of liquid biopsy type measures that may ultimately replace the conventional clinical chemistries that you’re running. Or, you know, they may not.

Dan Belsky, PhD: I think that we still don’t know how far that technology is going to go and how cheap it’s going to get, both of which will be important for determining whether they can replace the sort of standard toolkit that’s used in clinical medicine. But I think these biological aging clocks, speedometers, whatever they are, are not really here to replace the set of chemistries that you’re doing. They’re there to give you a new lens on a patient and to be an integrator of information from across the body. So you could put that together in the way that, you know, Morgan’s original blood chemistry PhenoAge does just from the standard panels that you’re running.

Dan Belsky, PhD: But we have a sense, I think, that these molecular clocks will do a better job at capturing that underlying aging process than a summary of clinical biomarkers. And they may be less sensitive to some of the perturbations that we worry about contaminating those other readings, including the medications we’re prescribing or variations in diet that are not consequential for the outcomes that we’re concerned with preventing, but may be influential of some of the biomarkers that we’re measuring. So again, it’s sort of like a noise reduction strategy. But ultimately at the moment, these things are at their best, they are compliments, not substitutes and it sort of remains to be seen how far we can go.

Dr. Kara Fitzgerald: So we continue to practice our best medicine, doing what we think is right and we can use these clocks as tools to, I don’t know, perhaps suggest how aggressive we need to be and so forth. I mean…

Dan Belsky, PhD: Well, and to identify people who need intervention and I think perhaps most powerfully, they may tell us how well these interventions are working at the person level.

Dr. Kara Fitzgerald: Yes.

Dan Belsky, PhD: You know, I can drug down my LDL. You know how to do that, but you don’t know whether giving me that statin is ultimately going to protect me as a living thing. You know it’s probably going to lower my risk of having a heart attack, but maybe not the next thing that’s going to get me. And so if we think about the medicine for aging in standard clinical medicine, it’s whack-a-mole. It’s just like, you know, this is wrong, I’m going to drug that. Wait, no, I’m going to drug that. But now I’m going to, you know… And then you end up with people who are 80 years old and on a dozen different medications and now the problem that you’re managing is actually the medication interactions, not the patient’s health problem. So the biological aging measurements that we are trying to develop, these whole organism measurements, I think are most useful in the context of patient management really for understanding whether the interventions you’re delivering are succeeding at moving the needle at the whole patient level rather than at the specific drug target.

Dr. Kara Fitzgerald: Yeah, that makes sense. And in functional medicine, our goal is to practice whole systems— We fancy that we’re the clinical application of systems biology, so we’re really looking at the whole person and so these tools are beneficial for us, and so with that individual with the elevated LDL, of course statin therapy may be appropriate, but they haven’t actually gotten off the couch in 20 years. So that’s probably going to be our first target, you know, things with data around them to at least improve health span.

Dan Belsky, PhD: I think in some ways, we were the choir you guys were preaching to, or people like me coming up, we’re reading this stuff and hearing the message that we aren’t just a bunch of mechanical parts that you can kind of rehab one at a time. We need strategies that maintain health at the whole person level. And I bought that all the way, but as an epidemiologist, I said, okay, so how do we measure whether those things are working? How do we figure out what the best path is? There wasn’t an endpoint that existed to summarize that success, other than they didn’t die, or they didn’t diagnose with a chronic disease, or they didn’t become disabled, all of which we don’t get to observe until really it’s too late to change course. So we wanted a measurement that would tell you whether the kinds of holistic interventions you’re delivering are having the effect that you want over time scales of months or years so that you can course correct, so that you can customize.

Dr. Kara Fitzgerald: Yes.

Dan Belsky, PhD: Like, if this exercise program isn’t working, let’s try more strength training, less cardio, we’re going to change the diet a little bit and see if that then gives us the response we want. In much the same way that oncologists or cardiologists deliver varying cocktails of drugs to manage the complex conditions that they’re seeking to manage. But your problem is not that there’s an organ that isn’t functioning properly or a group of cells that’s growing out of control, it’s that there’s this whole living thing that we want to keep in top functional shape for.

Dr. Kara Fitzgerald: In optimal… Yeah. That’s right, that’s right. And I think it’s motivating. I think the speedometer, I think the Pace of Aging, is highly motivating to individuals in our practice. It can gauge the intensity with which we’re going to argue for our protocols with a patient. And yeah, and give us feedback on whether we’re doing them correctly.

Dan Belsky, PhD: And they can see it, right? It’s not like you show them a whole sheet of labs and you’re like, see this number here? This one’s really telling you this and this one’s telling you this. There’s one number. Everybody understands this.

Dr. Kara Fitzgerald: Yeah. There’s a turtle, there’s a rabbit, you know… Yeah, it’s pretty cool.

Dan Belsky, PhD: I want to make it go slower.

Dr. Kara Fitzgerald: Yeah, exactly, yeah. How quickly can we see changes?

Dan Belsky, PhD: Yes, this is a great question. In terms of just the raw measurement itself, you can see changes really fast. Vadim Gladyshev’s lab, Jesse Poganek has a great paper in Cell Metabolism from a couple of years ago that shows that surgical intervention, so elective surgeries, really accelerate biomarkers of aging and then six months post-op, people are coming back to normal. In Jesse’s paper and also in a paper by Kieran O’Donnell that I think was published as a letter in response to the Paganic article, they’re looking at pregnancy and so we see dynamics in these clocks month to month during pregnancy. So certainly there can be a lot of dynamic change over short time intervals. What we don’t know, I think at this point, is whether that kind of short-term dynamic change we see is really fluctuating biological aging or some kind of bias arising from changes in the cellular composition of blood.

Dan Belsky, PhD: So we’re measuring DNA methylation marks. Those marks are part of cellular identity. I was just at an epigenomics conference where people were telling me, no, no, it turns out they’re not what defines cellular identity, but in the same way, five years ago, they were saying, no, no, no, it’s not a dimmer switch for the genome. It’s more complicated than that. So it’s definitely more complicated than that, but nevertheless, the methylation marks we measure are bound up in the particular type of cell that they’re derived from. And when we measure whole blood, it’s a mixture of monocytes, lymphocytes, granulocytes, and so in adults, you’re looking at maybe half neutrophils and more if somebody’s got an injury or something. But these different cell populations in blood fluctuate in response to injury, infection, conditions like pregnancy. And so, we don’t yet know the extent to which we can separate out the aging signal from the cell change signal.

Dan Belsky, PhD: We have pretty good methods for trying to back that out. And in Kieran’s paper, they show very nicely that even after they try, they do their best to control for changes in the cell composition of the blood, they still see some change over pregnancy. But I think that’s an open question. Now when it comes to intervention studies, where we’re directly acting on what we think are aging pathways, in CALERIE, we see change after 12 months. I think DO-HEALTH, which is a pan-European study, but Heike Bishoff-Ferrari has a paper in Nature Aging on the Swiss cohort within that larger trial. These were omega-3s, exercise and vitamin D in older people. I think that’s about the same kind of follow-up interval.

Dr. Kara Fitzgerald: Yes. Right.

Dan Belsky, PhD: Raghav Sehgal, who was a PhD student at Morgan’s before she left Yale for Altos, has a preprint up that has a whole bunch of interventional data that definitely suggests like six months may be a plausible time scale. But the answer is, we just don’t know. With the American Federation of Aging Research and Nir Barzalai and also Mahdi Moqri, who splits his time between Harvard and Stanford, we’re leading an initiative called FAST, which has not been going as fast as we’d like recently, but we’re really excited about. We’re trying to get blood out of freezers from completed clinical trials of interventions that Nir and his team have identified as having impacts on biology of aging in laboratory animals and which seem to have consequences, good ones, for all cause mortality in people.

Dan Belsky, PhD: And these trials very often have blood samples measured at three or six month intervals and the idea is that if we can assay those blood samples, we can then determine whether we’re seeing movement in these biomarkers over shorter time intervals. The advantage of these already completed clinical trials is that they have follow up to real FDA endpoints. So the extent that we observe an effect, we can evaluate, was this aging clock change that we’re observing, or aging speedometer change that we’re observing, actually consequential for the prevention of a disease end point or the prevention of death? So stay tuned, FAST is happening, if slightly slower than we want it to.

Dr. Kara Fitzgerald: That’s going to be incredibly helpful.

Dan Belsky, PhD: There’s more data coming soon and we’ll have a better answer for you, basically, is what I’m saying.

Dr. Kara Fitzgerald: Yeah, that’s awesome. That’s going to be wildly helpful. That’s great that you’re getting access to those banked specimen. Yeah, so push back on the clocks. I interviewed Matt Kaberlein a while ago. Yeah, you know… Is the fact that pregnancy accelerates aging or surgery accelerates aging… Is it? And by extension, push back on age reversal as a term. And I know that we’ve moved away from using that. And your comment, are we capturing the underlying biology of what drives aging and will ultimately kill us when we see these short-term changes?

Dan Belsky, PhD: Yeah, I mean, they’re good questions and far be it for me to argue with Matt. I got into this field reading his papers. And I think he’s been, you know, a trenchant and incisive critic of sort of “biomarker of the month” hype in aging research and I think his cautions are appropriate. I think that in some ways though, Matt’s reaction may be mostly to, kind of, the worst interpretations of the clocks rather than the way that they are being used in a lot of aging research today or the way we’re thinking about deploying them in clinical trials. It’s absolutely gotta be the case that before we trust the information we’re getting from these things, we establish that they in fact are predictive of the stuff that we care about and that when we change them, we change the things we care about. And the first of those questions we have evidence for, right? If you are looking at your DunedinPACE or your GrimAge, study after study shows us that when your pace is fast or your GrimAge is old, you are increased risk for disease, disability and death.

Dan Belsky, PhD: We don’t yet have the same evidence to show that when I intervene to slow DunedinPACE or to slow increase in GrimAge, that I am putting off the onset of disease. I think we’re beginning to see some studies suggestive of that interpretation. These are studies in which people have measured DNA methylation at multiple time points, and they can measure, in an observational context, not a randomized control trial, not an intervention, but in an observational context, they can measure whether we see change over time, and if that change is consequential for an endpoint we care about, like incidence of disease or mortality. And we do see some of that. I think that, you know, give us 12, 18 months and those studies will make it through peer review and you’ll have more of a literature to ground these interpretations. It’s still not good enough. We still need the trials with the outcome data, so that’s the motivation for FAST, is that until we can prove that an intervention that slows DunedinPace, actually prevents people from getting sick or dying, we won’t have a surrogate endpoint for evaluating the next generation of geroprotective interventions.

Dan Belsky, PhD: But for right now, I think we have enough evidence to believe that these are an interesting and important complement to other observations we can make about patients in the clinic or about ourselves if we’re sort of trying to personalize our own health and behavior. In saying these things about the clocks, in sort of boosting them in this way, I should also offer the caution that I think very differently about the way you and your colleagues may use these clocks to customize the interventions or the programs of behavior that you prescribe from how I think about biohackers or hobbyists doing the same thing, basically. The human body is not simple and if you break it, it’s going to be a problem. And so I think that when interpreted in the context of other observations of the body by a trained professional, these have the potential to be helpful. But I wouldn’t encourage anyone to go measure their clock and then immediately do something radical in response to it and then trust that measuring their clock a second time is going to tell them the truth. You really do need somebody who knows their stuff to be working with you to achieve the gains in knowledge or optimization in health that these clocks, at their best, could provide.

Dr. Kara Fitzgerald: Yeah, I think that’s interesting. So you’re not necessarily a fan of the Rejuvenation Olympics.

Dan Belsky, PhD: I think that when we built these tools— Before I got into aging research I was doing some genetics work and a question that always came up in genetics is, what if people don’t want to know? Like, maybe we shouldn’t let people have access to this information. And we got the same questions when we started measuring biological aging. Well, maybe people don’t want to know, maybe they shouldn’t know… And I think people should be able to know, you know, whatever we can measure but we should also offer them the caution that they may not necessarily be able to accurately interpret the information. And that if they want to make changes to their behavior or to supplements or drugs or other interventions they may undertake, they should consult with a healthcare professional.

Dan Belsky, PhD: And so, I think things like this are interesting. I don’t know that I would do many of the things that some of those people are doing to themselves. And many of the competitors are themselves quite sophisticated in their knowledge of human physiology. And many of them, I think, are also aided by healthcare professionals, perhaps some of your colleagues.

Dr. Kara Fitzgerald: Yeah. Sure.

Dan Belsky, PhD: So they’re not engaging in it unsupervised. So in that context, it doesn’t seem like that inherently of a problem. I think there are certainly cases where people may be overinterpreting values they’re getting from aging biomarkers and using them to motivate activities that may not be safe, but I’m not personally aware of any of those examples. And I’ll just say, the XPRIZE HealthSpan is actively trying to develop this class of interventions that we can prove to be safe and effective so people in some cases can take them on.

Dr. Kara Fitzgerald: Yes.

Dan Belsky, PhD: Yeah, I’m not at all advocating that people shouldn’t know, but I am suggesting that before you undertake any radical change in your lifestyle, certainly on the basis of one of these biomarkers, you consult with a physician or other healthcare professional.

Dr. Kara Fitzgerald: Sure. That absolutely makes sense. Certainly there’s just been a massive movement in medicine to make it available to patients. There was a time when everything was hidden and so I think we’re definitely moving in the right direction. But to your point, there’s an over-interpretation or a misinterpretation of some of the data that can motivate behaviors that aren’t necessarily healthy or helpful. And we do see that in functional medicine. We do see some individuals coming to us who are taking the sexiest cocktail of supplements, the biohacking recommended supplements, and have neglected to address their allergies or the cardiovascular disease. And we have seen that where the individual human, you know, really working with their components that need to be addressed and balanced is lost in just the bling of the biohacking era that we’re in. Not everybody.

Dr. Kara Fitzgerald: So going back to the CALERIE, you know, not everybody is meant to do fasting. Actually, this is one of the questions that came up as I was preparing for this interview. You saw what you consider a modest 2 to 3% change in the Pace of Aging. I think that’s actually pretty impressive. I mean, it’s correlated to quitting smoking, perhaps as impactful, just to give it context to the listeners. And the CALERIE trial, you can grab that paper on our show notes. So I think, perhaps… I don’t know, maybe you’re under…. Maybe you should give it a bigger shout out than saying it was only a modest change. But it prompted me to think too, what if you did subgroup analysis and who was optimal for a fasting intervention? And there’s a tool that will be available to us in the clinical setting that measures P16.

Dr. Kara Fitzgerald: And maybe looking at that particular protein, which if it’s really bottomed out in an individual, fasting is not a good thing and if it’s high, then yeah, maybe they’re ideal. It would be interesting to actually see if that made a difference in the Pace of Aging, if you distinguished some variable that… Because we see people who are doing one meal a day or who come to us on these really restrictive structures and we see pretty profoundly… Sometimes we see massive restoration of health and sometimes we see pretty profound imbalances. So there’s a necessary individualized component there. And then the other piece, of course, was that in the CALERIE study, they didn’t adhere to the full 25% restriction. So thoughts on that.

Dan Belsky, PhD: Yeah, so I mean, just to begin with the adherence question, the CALERIE investigators have come to the view that the reason people didn’t get to 25% was actually not a failure of willpower. It was actually an imprecision in the investigators model of how diets might need to change in order to achieve the target. But nevertheless, caloric restriction is really hard. And to the point of medical supervision, it’s not safe to do on your own without somebody monitoring you and advising you on your nutrition. If you want to cut 25% of the calories out of your diet, you need to be thoughtful about what you’re eating to begin with. You need to have someone who is measuring your blood to make sure that you’re getting the right levels of vitamins and minerals. And that was all done in CALERIE. You had a team of internal medicine specialists, dieticians, nutritionists, and psychologists working with these folks to help them reduce their diets in a safe way, reduce their caloric intake in a safe way, and make sure that they were not harmed by the intervention they were undertaking.

Dan Belsky, PhD: But to the question of this heterogeneity, clearly there were people in CALERIE who experienced dramatic slowing in their Pace of Aging, and there were people who were in the intervention group, whose Pace of Aging increased. And so in the paper we sort of show how much variation there is in response. Some people have suggested that it could be about genetic differences between people. I think, as you point out, the sort of combination of genetics and life history may have put people in a different physiological state at baseline that may have predisposed them to benefit or not from the intervention.

Dan Belsky, PhD: Within a trial like CALERIE, which is only a couple of hundred people, we don’t really have, in research terms, the statistical power to tease out who might have benefited most from the intervention. I think as we speak, I think this is still live, the National Institute on Aging has funded a series of planning grants that will ultimately provide the background for a new generation of CALERIE-like clinical trials and as we get the data back from those larger studies, we may be able to do a better job of identifying who in particular benefits or not. I think the P16 question is an interesting one. These folks are all healthy at baseline, so I suspect that you don’t have any of those kind of ultra-low P16 cases, but we don’t know, and unfortunately in CALERIE, because they did not sort the cells when they pulled the blood, we won’t know.

Dan Belsky, PhD: Because, at least according to Ned Sharpless [correction: Norman E Sharpless], and it’s maybe how you guys do it, you really want to measure P16 from lymphocytes and not sort of generically in whole blood. I mean, Ned also sort of measures them breast tissue and other tissues where they’re interested in cancer risk. But in CALERIE, I’m not sure that we’ll be able to get there, but it’s an interesting idea and we might ultimately, as molecular tools evolve, be able to better segment the participants on their pre-intervention biology in ways that illuminate who benefited most from the intervention on DunedinPACE or whatever the next generation of benchmark may be.

Dan Belsky, PhD: As to the final question, like effect size, as researchers, it’s our job to be conservative. We don’t want to run out there and say we cured cancer and then, you know, in the small print in mice.

Dr. Kara Fitzgerald: Yeah, right.

Dan Belsky, PhD: Or like, we had this massive effect on aging of…. three percent. But I think you’re right to point out that even this apparently modest slowing the Pace of Aging was consequential for people’s risk, at least as we estimated in studies where we observe their DNA methylation at time one and then follow them up for a decade or more to see when they get sick or how long they’ll live. So the amount of reduction in Pace of Aging that we observed in CALERIE corresponds to a 10 to 15% difference in risk of death over 15 years of follow-up in the Framingham Heart Study. This is what we reported in the paper. And that is about what you get from a smoking cessation intervention. So two years of dietary restriction is equivalent to quitting smoking for smokers and these people were healthy to begin with.

Dr. Kara Fitzgerald: Yeah, that’s impressive. Yeah.

Dan Belsky, PhD: Two years of caloric restriction though is serious business. We really want to get to a place where we can deliver that level of benefit with an intervention that is less challenging and requires less profound alterations to lifestyle. And so I think, obviously, the people who doing time restricted feeding, intermittent fasting, are very interested in that as a pathway and it may be that some combination, dietary intervention, exercise, other things can get us there without requiring us to do something that is quite as challenging as 25% CR.

Dr. Kara Fitzgerald: Yeah, well, even the consistency… Yeah. All right, so then I just want to circle back to pregnancy and surgery where it shows sort of accelerated aging, but then there’s a rebound at the end. And I know they kind of teased it out in the pregnancy paper, breastfeeding brought it back sooner, and I think higher weight was associated with less of a reduction. There’s certain variables. But if you’re continuously pregnant, okay, forever, which obviously isn’t going to happen physiologically, perhaps that’s going to result in true accelerated aging, but what I’m getting at here is this idea of— and you’ve been touching on this in various ways— aging as a programmed thing, as a programmed phenomena that’s consistent. And I think, versus…

Dr. Kara Fitzgerald: Well, a friend of mine, Josh Mitteldorf, sort of talks about two tracks. He talks about the program phenomena and then he talks about damage. Damage from smoking, damage from being exposed to toxins, like all of the things we know that are going to wreak havoc on health span and prompt the development of diseases, perhaps earlier than we would if we’re just on the programmed aging phenomena and living in a bubble and super clean. And I think the argument for programmed aging— Well, I think you were kind of touching on it, so something underlying and shared. But the new mammalian clock, you know, the lifespan clock, Vittorio Sebastiano, who’s been on this podcast before, these guys are all looking at polycomb recessive complex clocks, which are ticking and on in utero and really tracking with development across time and are arguing that the phenomena of development includes aging and death. And so now across mammals, you can use one of these polycomb recessive complex clocks and demonstrate lifespan, which is pretty extraordinary.

Dr. Kara Fitzgerald: And [Steve] Horvath is an author on these papers, but they use this idea, they call it pseudo-programmed aging— This seems to me like to be a program. I’m not sure about the pseudo component— And maybe, some of those CPGs that you guys are looking at are correlative to something that happens across mammals or is going to consistently drive the aging journey regardless of how cleanly you’re living. Actually, just going back to the Sebastiano clock, they use it to measure cellular rejuvenation, so the Yamanaka factors really manipulate that clock. And we know that if a cell is exposed to Yamanaka factors long enough, it’s going to go back to a pluripotent stem cell, so this clock that they’re using is picking up a real fundamental aging phenomena.

Dan Belsky, PhD: Yeah, so let me first address this question of programming. I think that saying something is regular and saying it’s programmed are not necessarily the same thing. In gerontology, aging as a program has a history and this idea that maybe there’s something programmed about senescence, maybe there’s a genetic program, just like the one that builds us up into reproductively mature organisms, that ultimately winds us down so that we die. I guess my read of the field is that we’ve kind of rejected that hypothesis and that aging is not that kind of a program. But it’s absolutely true that aging exhibits really important regularities, including signs of this loss of information, as David Sinclair calls it, or damage accumulation, as Vadim Gladyshev calls it, from the very beginnings of life. And I think that, at least the way we think about it, is as an entropic process.

Dan Belsky, PhD: Our DNA encodes a program that assembles life from biochemical elements, builds a reproductively viable agent, and then tries to keep that thing running as long as it can. But it cares less and less. This is sort of selection shadow, the evolutionary biology argument around aging. The reason we get sick and die is that evolution stops caring about us so much once we stop reproducing and maybe we get a little bit of a bump from doing some parenting, even some grandparenting, but ultimately, you know, our genes are out there, evolution doesn’t care anymore.

Dan Belsky, PhD: Meanwhile, you know, the universe is trying to tear us apart from the very beginning. Entropy is not a biological principle, it’s physics. And that breakdown is going to occur at some baseline rate, no matter what and that’s sort of what you’re talking about, I think, as programmed and other people sometimes refer to as intrinsic aging. And I think biologists like that idea because they study cells in a dish or worms or flies or mice who live under these controlled conditions for whom there is no environmental variation, and so that’s what they’re inclined to think about is, what is this thing that’s happening? But I don’t think of the environmental drivers of aging as a qualitatively different process. They too contribute to that entropic disintegration of our biology, the breakdown of our bodies that overwhelms the genetic program that’s trying to assemble us and keep us together.

Dan Belsky, PhD: And so Vadim has written a lot about how the basic processes of living cause molecular damage. Cellular metabolism produces molecular damage, and so just by living a cell is aging. So that could be an explanation for this underlying rate that we’re experiencing. But of course, if you stress the cell and it has to live harder, it’s going to accumulate damage faster and that’s exactly what things like smoking or air pollution, or extreme heat, or psychological stress are doing to our bodies. They’re making us live harder and that is accelerating the accumulation of molecular damage, even as in addition, in some cases we may have toxicants entering our body from the environment and causing physical damage to cells on their own.

Dan Belsky, PhD: So I guess this is now probably deeper water than I ought to be swimming in. I’m not a biologist, but my read is that we’re looking at one thing and that we ought not to try and separate an underlying aging process from what we observe as aging induced by environmental causes. It’s ultimately all about the maintenance of integrity in the functioning of our cells and our tissues and our organs. And those things will accumulate damage simply by running on their own, and they will accumulate damage faster if we stress them. And there’s going to be genetic variation in the efficiency and effectiveness of our damage repair processes, and even in our sort of assembly of those tissues and organs. But I don’t think of it as two different things.

Dr. Kara Fitzgerald: Interesting. Okay. All right. Fair enough. Just going back to pregnancy, because I don’t want anybody to leave this thinking, yeah, pregnancy is bad. It’s an age accelerant, and therefore it’s a bad thing and it’s contributing to aging. I mean, obviously, it’s like a scale. The joys of being a parent are anti-aging, I think, ultimately. Well, it can be. I mean, there’s going to be a give and take in this journey, big time. And yeah, go ahead.

Dan Belsky, PhD: Yeah, so on the pregnancy side, again, I think what we see in terms of observing accelerations and decelerations of aging over pregnancy, I would not take seriously yet. From a research perspective that’s interesting. From the, sort of, I’m managing my own health perspective, I think it’s irrelevant. There are data, my colleague, Calen Ryan, published a paper last spring close to the O’Donnell paper, about how gravidity, the number of pregnancies a woman has had, relates to her biological aging on these epigenetic clocks. And so there is some evidence that having a lot of kids is associated with accelerated aging.

Dr. Kara Fitzgerald: It’s a U curve, I believe. Is that right?

Dan Belsky, PhD: Well, so being nulliparous, not ever having been pregnant, is associated with somewhat faster aging. But I think we should think about that in much the same way we think about the early studies of alcohol use, where abstainers had worse outcomes than people who drank modest amounts of alcohol. And the modern epidemiology of the phenomena suggests that the reason we observe that association is that the people who don’t drink are different from the people who do. They are enriched for people who don’t drink because they’re ill and so that’s why we see that increased risk. And I’m inclined to interpret the somewhat accelerated aging among women who have not had pregnancies as reflecting that kind of a process where the reason they haven’t had a pregnancy is because of some other cause that is also accelerating their aging.

Dr. Kara Fitzgerald: It makes sense. Yeah.

Dan Belsky, PhD: Now, it remains to be seen if that turns out to true, but I would interpret with caution these U-shaped or J-shaped curves around exposures where sometimes the people not doing the thing at all are just different in a way that might suggest there’s another cause.

Dr. Kara Fitzgerald: Yeah, that makes sense. And I am not intentionally, sort of, zeroing in on pregnancy. I think what I’m really trying to say more broadly is that for the short term, certain experiences are going to just ramp things up and if you happen to get your Pace at that time, it may be higher than you’re happy about. But it may be just that there’s a parent dying and you’re involved in some really stressful medical management and it’s emotional, et cetera. So you see these short term bumps that are just reflecting the journey of life, but will level out once you get to the other side.

Dan Belsky, PhD: Yeah, and ultimately we may learn that there are times when you want to take these tests and times when you don’t in much the same way that you don’t take somebody’s CRP if you they have an active infection. Or at least you don’t interpret the value.

Dr. Kara Fitzgerald: Yeah. That’s right. In context.

Dan Belsky, PhD: You know, we fast people before we measure a bunch of stuff and so, as you say, it may be the case that pregnancy is a case where we don’t want to interpret these aging clock values or periods of extreme stress. It could be useful to measure them during periods of extreme stress. Oh, this is really doing a number on you. We want to maybe deliver some mitigating services or interventions. But that’s all to be learned, particularly as we move these tools into clinical settings and as clinicians like yourself and your colleagues accumulate data that can form a knowledge base for us to better understand when these things are interpretable and useful and when they’re not.

Dr. Kara Fitzgerald: They’re fun to use in practice in the context of an overall approach. I think it can be really motivating and for patients they can be validating. They can be a little anxiety-provoking, but motivating, you know, just depending on what we see. So I do think they’ve been just a really nice addition to our toolkit, but there are a lot of changes and they can be confusing. I just want to end, you know we’ve been talking for a while, with anything that you want to add to the conversation, but also the frontiers and here we’re heading in geroscience. What should we be looking for in clinical practice to be thinking about incorporating?

Dan Belsky, PhD: Yeah. I think when I look into the sort short term future, I’m really thinking about much more interventional data.

Dr. Kara Fitzgerald: Yes.

Dan Belsky, PhD: Right now, I think that if you want to do risk stratification, we have a toolkit that you can trust. But if you do something and say, oh, my GrimAge didn’t respond. Does that mean it didn’t work? Maybe not. And so we’re learning a lot and I think we’re seeing the acceleration now. There will be a bunch of trials published in the next year or two about which of these biomarkers are likely to respond to intervention and which won’t. And there may be some biomarkers more sensitive to different kinds of interventions, and on the back of that work about responsiveness is going to come work about the impact of the response. So that’s a thing that I would keep a close eye on so that you can advise patients on which of these biomarkers may be most useful for understanding where I’m at now and which may be most useful for understanding how is the program of behavior change or therapy that I’m undertaking kind of moving the needle for me. I think that we are seeing the birth of a field of proteomic aging assessment. And I think the liquid biopsy thing seems to have real potential in that space.

Dan Belsky, PhD: So right now, we’re still in the very early days of that field. There’s a lot of hype. There are a lot of papers making strong claims about the utility of the metrics that are being developed. What we don’t yet have in the proteomics literature are other teams following up tools that other investigators have developed. And that’s really when epigenetic clockwork began to mature and deliver real value, I think, at the level of population, public health, but now eventually into the clinic, is when people are taking the tool off the shelf, putting it into their study and asking the question and getting an answer consistent with what the original investigators got. That’s really a thing that I’m looking for in the proteomic space and also I’m looking for robust evidence of the specificity of some of these tissue or organ specific measurements.

Dr. Kara Fitzgerald: Yes.

Dan Belsky, PhD: And then I think, you know, maybe a third trend is— And we’re early days here, we’re very early days here— but we know that aging is a nonlinear process. We know that mortality is an exponential process, right? Risk doubles every eight years or so from the age of thirty on. Michael Snyder recently made a lot of news publishing some molecular data suggesting that there are these sort of periods in the human lifespan when aging accelerates, there’s sort of a phase shift. And this echoes some work that Tony Wyss-Coray’s group had published a couple of years earlier.

Dr. Kara Fitzgerald: We’ll find it.

Dan Belsky, PhD: But in any case, having these models, if we can build good ones, will dramatically improve your capacity to advise individual patients on how their clock readouts or other tools reflect where they are in that process. And we talk about personalizing intervention, but we may, to some extent, also need to personalize some of these measurements of aging based on where a person is in the lifespan. So I’ll be looking to see how that work matures. If these observations that have come out of studies that are mostly comparing people of different ages are borne out in longitudinal studies that are tracking the same people over time. Do we see this up and down at regular intervals in the human lifespan and is that going to inform the way we build these tools and the way we interpret values on them?

Dan Belsky, PhD: If a person said oh, I’m aging fast, and it could be like, well, actually, at this stage in life, that’s pretty typical and so it’s not a five alarm fire. Sure monitor it, but don’t freak out. And there’s actually just a really impressive paper, again from Vadim Gladyshev’s lab, his PhD student, Kezhen Ying, who just defended his dissertation and is now Dr. Ying, in which they try to disentangle age-correlated DNA methylation marks that reflect the accumulation of damage, the bad stuff we want to prevent, from signs of adaptation, the resilience to aging that we would want to encourage. But I would not conflate development, rapid growth, with the aging process, even though that may also be rapid. So if you take Vadim seriously, what he’s telling us is that if you are making something grow really fast, if you’re doing a lot of cellular work, you’re going to cause a lot of cellular damage. So you are going to see aging rising in parallel with development, but they’re not the same thing.

Dr. Kara Fitzgerald: Right. Yeah, that’s right. Especially if we’re going back to your original definition of aging as being the damage phenomena. So yeah, OK.

Dan Belsky, PhD: At least the aging that we are trying to slow down and prevent is the damage phenomenon.

Dr. Kara Fitzgerald: Yeah, for sure. Okay. Well, listen, thank you so much. That was a roller coaster of a ride. Very interesting. Anything to add or did we, I think we hit—

Dan Belsky, PhD: I think we covered it all.

Dr. Kara Fitzgerald: This will be a ton of food for our listeners. Folks, we’ll definitely just pop as many of these references into the show notes so you can grab them and read them. I think quite a few of them are open source. Thanks, Dan. Thanks for joining me on New Frontiers.

Dan Belsky is Associate Professor of Epidemiology at the Columbia University Mailman School of Public Health in the Robert N Butler Columbia Aging Center, where he directs the Center’s Geroscience Computational Core. His work seeks to develop methods to measure the pace and progress of biological aging in humans and to use these methods to identify drug, behavior, and policy interventions that can address disparities in healthy aging and increase healthy lifespan for all.

Daniel W. Belsky PhD.

Dunedin Longitudinal Studies

Research: Quantification of biological aging in young adults

Bio-Age Lab Test Package

Research: Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial

Article: To promote healthy aging, focus on the environment

Research: DunedinPACE, a DNA methylation biomarker of the pace of aging

Article: Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

Research: DNA methylation age of human tissues and cell types

Article: Aging Rate Indicators: Speedometers for Aging Research in Mice

Research: Biological age is increased by stress and restored upon recovery

Research article: Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders

DO-HEALTH Clinical trial

Research Article: Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial

Research Article: Cells exhibiting strong p16^INK4a promoter activation in vivo display features of senescence

Research Article: Pregnancy is linked to faster epigenetic aging in young women

Article: Nonlinear dynamics of multi-omics profiles during human aging

Article: Ageing hallmarks exhibit organ-specific temporal signatures

The Framingham Heart Study

Professor Reremoana Theodore

Professor Richie Poulton

Terrie Moffitt, PhD

Avshalom Caspi, Ph.D

Gladyshev Lab

Dr. Raghav Sehgal

Nir Barzalai, MD

Mahdi Moqri, PhD, MDA

Josh Mitteldorf

David Sinclair, A.O., Ph.D.

Blog interview: Past, Present, and Future of “Biological Aging” with Dr. Fitzgerald

Podcast: Decoding Aging: The Science Of Cellular Rejuvenation With Dr. Vittorio Sebastiano

Podcast: You Are Only As Young As Your Immune System with Dr. Greg Fahy

Podcast: Measuring Longevity: Latest Bio Age Research with Dr. Morgan Levine

Podcast: Understanding Genetics of Aging with Harvard Professor Dr. David Sinclair

Video Blog: Does Multivitamin Use Increase Mortality Risk?

DrKF Clinic: Patient consults with DrKF physicians including Younger You Concierge

Bio Age Lab Test

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